title: Adverse events and discomfort in studies on healthy subjects: the volunteer's perspective. A survey conducted by the German Association for Applied Human Pharmacology.
abstract: OBJECTIVE
  The various good clinical practice (GCP) guidelines do not define the volunteering subject as an active party. The present survey addresses the volunteer's perception of study-related inconvenience and risk and its impact on their decision to enroll.
  
  
  METHODS
  The survey consisted of a questionnaire to be filled out voluntarily and anonymously by healthy subjects who volunteered for enrollment in human pharmacology studies and who had participated in at least one previous study. Twenty-five categorised multiple-choice questions covered previous study experience, motives for volunteering, perception of and compliance with study directives and restrictions, past experience with adverse events, impact of the study environment on perceived well-being and the nature of adverse events likely to discourage them from enrollment.
  
  
  RESULTS
  Seven centres contributed by providing at least 30 (range 30-100) evaluable questionnaires. The database consists of a total of 440 healthy subjects (30.5% females, 69.5% males), from 18 to over 60 years of age. Two hundred and seven subjects (47.1%) were company employees and 233 (52.9%) were external volunteers. Eighty nine percent only participated in studies at one particular centre. Some 53.3% indicated financial motives, 27.8% 'contribution to an improvement of pharmacotherapy', 12.7% 'social responsibility', while 6.2% indicated other motives, mainly the opportunity of a free medical check-up. Thirteen subjects (3%) admitted to not answering correctly to the recruitment questions; this limited reliability is suspected to be even larger when the answer might preclude enrollment. From the volunteers' perspective, the environmental study conditions clearly appeared to have a highly relevant impact on their personal well-being. Some 17.1% of the subjects reported to have suffered adverse events occasionally and 2.7% frequently; but 14% admitted not reporting adverse events promptly and about 20% indicated that, with respect to previous adverse events, they first sought advice from other volunteers rather than from the investigator.
  
  
  CONCLUSIONS
  Adverse events and inconveniences are inherent to nontherapeutic studies in healthy subjects. From the volunteer's perspective it appears that the incidence of adverse experiences in such studies exceeds the reported frequencies from investigators considerably. This finding suggests that investigators are usually not aware or able to ascertain the true incidence of adverse events. The present survey also confirms that pertinent information on the personal history may be unreliable. Volunteers are reluctant to answer questions regarding, in particular, their smoking habits, caffeine and alcohol consumption. Regarding the matter of informed consent, a noteworthy contradiction between the volunteers' attitude and behaviour became apparent. Although the volunteers admit that even rather minor adverse events ordinarily would discourage them, they still consent to enrollment. In view of this apparent contradiction, there is no alternative to the investigator's personal responsibility to counsel and protect the subject. Surveys such as this one may contribute to the awareness that the explicitness of GCP guidelines merely define the format, but not the content quality of these fundamental ethical values, which remain the unique burden and challenge of the investigator.
authors.affiliation: Department of Clinical Pharmacology, Corporate Research, Frankfurt/Main, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hermann
authors.forename: D
authors.initials: D
authors.lastname: Heger-Mahn
authors.forename: M
authors.initials: M
authors.lastname: Mahler
authors.forename: M
authors.initials: M
authors.lastname: Seibert-Grafe
authors.forename: C
authors.initials: C
authors.lastname: Klipping
authors.forename: K
authors.initials: K
authors.lastname: Breithaupt-Grögler
authors.forename: C
authors.initials: C
authors.lastname: de Mey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009042:Motivation